TABLE A1.

All-Causality AEs Occurring in ≥10% of Patients in Any Treatment Group

Event	Lorlatinib (n = 149)			Crizotinib (n = 142)
	Any Gradea	Grade 3	Grade 4	Any Gradeb	Grade 3	Grade 4
Any AE, No. (%)	149 (100)	95 (64)	20 (13)	140 (99)	69 (49)	12 (8)
Hypercholesterolemiac	108 (72)	30 (20)	2 (1)	5 (4)	0	0
Hypertriglyceridemiac	99 (66)	25 (17)	12 (8)	8 (6)	0	0
Edemac	85 (57)	6 (4)	0	61 (43)	2 (1)	0
Peripheral neuropathyc	65 (44)	2 (1)	0	23 (16)	1 (1)	0
Weight increased	65 (44)	34 (23)	0	18 (13)	3 (2)	0
Fatiguec	45 (30)	2 (1)	0	47 (33)	4 (3)	0
Arthralgia	41 (28)	1 (1)	0	20 (14)	0	0
Cognitive effectsc	41 (28)	5 (3)	0	10 (7)	0	0
Hypertension	39 (26)	18 (12)	0	6 (4)	1 (1)	0
Anemia	37 (25)	6 (4)	0	14 (10)	4 (3)	0
Diarrhea	34 (23)	3 (2)	0	75 (53)	1 (1)	0
Dyspnea	34 (23)	5 (3)	0	26 (18)	4 (3)	0
Headache	33 (22)	0	0	28 (20)	1 (1)	0
Mood effectsc	31 (21)	2 (1)	0	9 (6)	0	0
Cough	30 (20)	0	0	27 (19)	0	0
Pyrexia	30 (20)	1 (1)	0	19 (13)	2 (1)	0
ALT increased	29 (19)	4 (3)	0	49 (35)	5 (4)	1 (1)
Back pain	29 (19)	2 (1)	0	20 (14)	0	0
Constipation	29 (19)	0	0	43 (30)	1 (1)	0
Vision disorderc	29 (19)	0	0	57 (40)	1 (1)	0
Pain in extremity	28 (19)	0	0	14 (10)	0	0
Gamma-glutamyltransferase increased	27 (18)	8 (5)	1 (1)	22 (15)	6 (4)	0
Nausea	25 (17)	1 (1)	0	75 (53)	3 (2)	0
SARS-CoV-2 test positive	25 (17)	0	0	3 (2)	0	0
AST increased	24 (16)	3 (2)	0	39 (27)	5 (4)	0
Lipase increased	22 (15)	8 (5)	1 (1)	18 (13)	4 (3)	1 (1)
Hyperglycemia	21 (14)	8 (5)	0	5 (4)	0	0
Myalgia	21 (14)	0	0	6 (4)	0	0
Vomiting	20 (13)	1 (1)	0	56 (39)	2 (1)	0
Blood creatine phosphokinase increased	19 (13)	4 (3)	0	25 (18)	5 (4)	1 (1)
Dizziness	19 (13)	0	0	21 (15)	0	0
Sleep effectsc	19 (13)	1 (1)	1 (1)	14 (10)	0	0
Chest pain	18 (12)	2 (1)	0	20 (14)	1 (1)	0
Rash	18 (12)	0	0	12 (8)	0	0
Upper respiratory tract infection	18 (12)	1 (1)	0	11 (8)	2 (1)	0
Amylase increased	17 (11)	0	0	19 (13)	1 (1)	0
Pneumonia	17 (11)	5 (3)	1 (1)	13 (9)	4 (3)	1 (1)
Hyperlipidemia	16 (11)	2 (1)	1 (1)	0	0	0
Hyperuricemia	16 (11)	0	1 (1)	6 (4)	0	0
Blood creatine increased	11 (7)	2 (1)	0	22 (15)	3 (2)	0
Neutropenia	11 (7)	1 (1)	0	21 (15)	13 (9)	0
Blood alkaline phosphatase increased	9 (6)	0	0	17 (12)	2 (1)	0
Dysgeusia	9 (6)	0	0	23 (16)	0	0
Hypoalbuminemia	8 (5)	1 (1)	0	18 (13)	6 (4)	0
Decreased appetite	6 (4)	0	0	35 (25)	4 (3)	0
Sinus bradycardia	6 (4)	0	0	16 (11)	1 (1)	0
Blood lactate dehydrogenase increased	5 (3)	1 (1)	0	16 (11)	0	0
Bradycardia	4 (3)	0	0	20 (14)	0	0
Neutrophil count decreased	3 (2)	0	0	18 (13)	8 (6)	4 (3)

Abbreviation: AE, adverse event.

^a Fourteen patients in the lorlatinib group died due to COVID-19 pneumonia (n = 2), respiratory failure (n = 2), pneumonia (n = 1), cardiac failure (n = 1), pulmonary embolism (n = 1), lower respiratory tract infection (n = 1), basal ganglia hemorrhage (n = 1), cardiac arrest (n = 1), cardiac failure acute (n = 1), death (n = 1; reason unknown), disease progression (n = 1), or lung neoplasm malignant (n = 1). Two treatment-related deaths occurred due to cardiac failure acute and respiratory failure (n = 1 each).

^b Seven patients in the crizotinib group died due to malignant neoplasm progression (n = 2), pericardial effusion (n = 1), death (n = 1; reason unknown), disease progression (n = 1), neoplasm progression (n = 1), or Clostridium difficile colitis (n = 1).

^c This category comprised a cluster of AEs that may represent similar clinical symptoms or syndromes.